Human dihydroorotate dehydrogenase (DHODH) is an integral protein of the inner mitochondrial membrane (IMM) that catalyzes the fourth step of the de novo pyrimidine biosynthesis, and is functionally connected to the respiratory chain via ubiquinone Q10. Human DHODH is a well validated target for anti-inflammatory drugs and mutations in human DHODH have been identified as the cause of Miller syndrome, a rare genetic disease.
This project aims to investigate the mechanism of DHODH in a non-crystalline, physiologically relevant membrane-bound state using neutron reflectometry in combination with other appropriate measurement techniques. By using a novel combination of recombinant protein production and deuterium labeling of lipids in yeast cell cultures, we will characterize the orientation and conformation of DHODH reconstituted in mitochondrial membrane mimics, the mechanisms of substrate/inhibitor binding as well as the effects caused by mutations causing Miller syndrome. The project is a close collaboration with the European Spallation Source (ESS) in Lund and the Institut Laue Langevin (ILL) in Grenoble, France, and will involve stays at both facilities.
The insights and methods developed in this project will further be applied to a number of test cases in which protein-lipid interactions with relevance to human health are studied using neutron reflectometry.
Lund University was founded in 1666 and is repeatedly ranked among the world’s top 100 universities. The University has 42 000 students and 7 400 staff based in Lund, Helsingborg and Malmö. We are united in our efforts to understand, explain and improve our world and the human condition.
The Faculty of Science conducts research and education within Biology, Astronomy, Physics, Geosciences, Chemistry, Mathematics and Environmental Sciences. The Faculty is organized into ten departments, gathered in the northern campus area. The Faculty has approximately 1900 students, 330 PhD students and 700 employees.
Type of employment: Temporary position longer than 6 months; Limit of tenure, four years according to HF 5 kap 7§
First day of employment: October 1, 2017, or according to agreement
Salary: Monthly salary
Number of positions: 1
Working hours: 100 %
Reference number: PA2017/908
Undergraduate education (Masters degree) in Molecular Biology, Biochemistry, Biotechnology, Chemistry or equivalent (the applicant’s undergraduate education should include a significant proportion of chemistry, molecular biology, microbiology and biochemistry).
Previous experience with analytical chemistry methods, lipid membranes, molecular biology techniques, cell culture techniques and recombinant protein production is highly desirable, as well as with techniques that will be used in the project (LC, HPLC, GC, NMR and mass spectroscopy).
Specific experience with one or more of the following represents an advantage:
The successful candidate must have a track record of working independently, with a demonstrated ability to analyze and present scientific data.
Fluent spoken and written English is an absolute requirement, as are good record-keeping and practical skills in the laboratory. The successful candidate will work with the Lund Protein Production Platform (LP3) and the DEMAX platform of the European Spallation Source (ESS) in Medicon Village, and therefore the ability to adapt to the local safety practices and established work routines and a commitment to working synergistically and in teams with others is crucial. This project is a close collaboration between Lund University, ESS and the Institut Laue Langevin (ILL), Grenoble (France) and will involve travel to ILL in Grenoble for at least two months per year and potentially to other neutron facilities to carry out experiments.
Special requirements for this position
Previous experience of working with cells or microorganisms at the cellular and molecular level is required or alternatively previous experience of lipid extraction and characterization using analytical chemistry/chromatography methods. Good analytical and mathematical skills are essential for the neutron scattering work. Fluent spoken and written English is an absolute requirement. A demonstrated ability to use and analyse scientific literature as well as to write scientifically are required (e.g. diploma or Master thesis, project report or similar). Previous peer-reviewed publications are an advantage. Previous experience of relevant X-ray or neutron scattering methods is an advantage.
The ability to spend a couple of months per year at the ILL and to travel to experiments at other neutron facilities, as well as to work evenings/weekends during experiments is an absolute requirement. EU citizenship is an advantage, but is not required.
Students with basic eligibility for third-cycle studies are those who- have completed a second-cycle degree- have completed courses of at least 240 credits, of which at least 60 credits are from second-cycle courses, or- have acquired largely equivalent knowledge in some other way, in Sweden or abroad.
The employment of doctoral students is regulated in the Swedish Code of Statues 1998: 80. Only those who are or have been admitted to PhD-studies may be appointed to doctoral studentships. When an appointment to a doctoral studentship is made, the ability of the student to benefit from PhD-studies shall primarily be taken into account. In addition to devoting themselves to their studies, those appointed to doctoral studentships may be required to work with educational tasks, research and administration, in accordance with specific regulations in the ordinance.
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Reference number: PA2017/908
Last application date: 15. May 2017 11:59 PM CET